An integrated optical waveguide based surface plasmon resonance biosensor is formed by detecting amplitude and phase of electromagnetic waves utilizing interferometry and/or optical delay configurations.
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17. An apparatus, comprising:
one or more optical channels, comprising a planar wave-guide based configuration and arranged as an array of wave-guide surface plasmon resonance (spr) sensors, wherein each said spr sensor that further comprises:
a substrate,
a core layer,
a cladding arranged to surround said core layer and operatively attached to said substrate, wherein said core layer and said cladding operate as a waveguide,
a trench sensing area, further comprising, a first material, a metal layer operatively attached to said first material, a buffer layer operatively attached to said metal layer, a capture layer operatively attached to said buffer layer, and
wherein a raised portion of said cladding defines a reservoir above said capture layer; and
wherein an optical waveguide arrayed grating is capable of being operatively coupled to each said sensor for spectral interrogation of an spr response.
7. An apparatus, comprising:
one or more optical channels arranged in an optically delayed planar waveguide based configuration, wherein at least one of said optical channels includes a surface plasmon resonance (spr) sensor that further comprises:
a substrate,
a core layer,
a cladding arranged to surround said core layer and operatively attached to said substrate, wherein said core layer and said cladding operate as a waveguide,
a trench sensing area, further comprising, a first material, a metal layer operatively attached to said first material, a buffer layer operatively attached to said metal layer, a capture layer operatively attached to said buffer layer, and
wherein a raised portion of said cladding defines a reservoir above said capture layer; and
wherein at least one of said optical channels includes a spr sensor arranged as a reference sensor; and
wherein one or more optical arrayed waveguide gratings are capable of being operatively coupled to a predetermined sensor for spectral interrogation of an spr response of a said predetermined sensor.
1. An apparatus, comprising:
one or more optical channels, comprising a planar wave-guide based configuration and further comprising at least one Mach Zehnder (MZ) interferometer arrangement, wherein at least one of said optical channels includes a surface plasmon resonance (spr) sensor that further comprises:
a substrate,
a core layer,
a cladding arranged to surround said core layer and operatively attached to said substrate, wherein said core layer and said cladding operate as a waveguide,
a trench sensing area, further comprising, a first material, a metal layer operatively attached to said first material, a buffer layer operatively attached to said metal layer, a capture layer operatively attached to said buffer layer, and
wherein a raised portion of said cladding defines a reservoir above said capture layer;
wherein at least one of said optical channels includes a spr sensor arranged as a reference sensor; and
wherein an optical waveguide arrayed grating is capable of being operatively coupled to a predetermined sensor for spectral interrogation of an spr response.
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This application claims the benefit of U.S. Provisional Application No. 60/424966, filed Nov. 8, 2002, and entitled, “Multiple Array Surface Plasmon Resonance Biosensor,” which is incorporated herein by this reference.
1. Field of the Invention
The present invention relates to biosensors based on integrated optical waveguides, and more particularly, to surface plasmon resonance interferometric detection sensors formed by an array of planar waveguides.
2. Description of Related Art
Surface plasmon resonance (SPR) devices have shown high sensitivity in the detection of chemical and biological agents. Conventional SPR devices are based on sensing the reflectance change of mono- or polychromatic light, which undergoes total internal reflection at the hypotenuse of a prism, which is coated with a thin metal film. At certain angles of incidence for a given wavelength of light, the incident light with polarization in the plane of incidence is in resonance with the surface plasmon of the metal film. The term “surface plasmon” describes the collective longitudinal oscillation of the electrons in the metal film. The angle of incidence for the wavelength of the light at which this surface plasmon resonance occurs is very sensitive to the dielectric constant of the immediate environment of the thin metal film, which can be changed by a change in the index refraction of the surrounding material or chemical bonding of material deposited onto the metal layer.
Free space SPR interferometry techniques, such as SPR ellipsometry, optical heterodyning, and mapping the spatial intensity distribution, are cumbersome to be incorporated into compact SPR devices and exhibit high sensitivity to changes in the environment, such as temperature fluctuations. By contrast, a planar optical waveguide based SPR sensor operates similarly as a free space prism SPR device, but it offers higher sensitivity and is capable of being fabricated into multiple sensors on a single chip and can be easily integrated with fiber optical components, such as light sources and detectors.
Background information on a waveguide based SPR sensors that monitors the ratio of the transverse magnetic (TM) polarization and transverse electric (TE) polarization intensities is described in U.S. Pat. No. 5,606,633, issued Feb. 25, 1997, to Groger et al. “Chemical detector employing surface plasmon resonance excited using an optical waveguide configuration as an asymmetric waveguide coupler,” including the following, “the ratio of the TM and TE polarization intensities is monitored by a polarization beam splitter. The relatively unchanged TE polarization intensity serves as an integral reference for the sensor.”
The article “Surface plasmon resonance biosensor based on integrated optical waveguide” by J. Dostalek et al. (Sensors and Actuators, vol. B76, 2001, pages 8–12) describes the use of a broadband light source combined with spectral interrogation of SPR and demonstrates a detection sensitivity of 10−6 to a change in the index of refraction. Another SPR technology is based on detecting the phase-change of the light in a SPR sensor, which has been shown to significantly increase the detection sensitivity (P. Nikitin et al, “Surface plasmon resonance interferometer for biological and chemical sensing” Sensors and Actuators B., 1999, vol. 54, pp. 43–50).
Accordingly, a need exists to provide a highly sensitive surface plasmon waveguide arrayed sensor that simultaneously detects intensity and phase by planar light wave geometries. The present invention is directed to such a need.
Accordingly, the present invention provides a highly sensitive surface plasmon waveguide apparatus arranged in a planar waveguide Mach Zehnder based configuration for measuring adsorbed monolayers of predetermined solutions.
Another aspect of the present invention is to provide a highly sensitive surface plasmon waveguide sensor apparatus arranged in a planar waveguide optically delayed waveguide based configuration for measuring adsorbed monolayers of predetermined solutions.
A final aspect of the present invention is to provide a highly sensitive surface plasmon waveguide sensor apparatus arranged as an array of wave-guide surface plasmon resonance (SPR) sensors operatively coupled to optical waveguide arrayed gratings for measuring adsorbed monolayers of predetermined solutions.
Accordingly, the present invention provides a highly sensitive waveguide sensor capable of measuring one or more monolayers of bio-agents and/or chemical agents for immunoassay or other receptor and analyte reactions.
The accompanying drawings, which are incorporated into and constitute a part of the specification, illustrate embodiments of the invention and, together with the general description of the invention given above, and the detailed description of the specific embodiments, serve to explain the principles of the invention.
The detailed description of the specific embodiments, together with the general description of the invention, serves to explain the principles of the invention.
Unless otherwise indicated, all numbers expressing quantities of ingredients, constituents, reaction conditions and so forth are to be understood as being modified in all instances by the term “about”. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification are approximations that may vary depending upon the desired properties sought to be obtained by the subject matter presented herein. At the very least, and not as an attempt to limit the application of the doctrine of equivalents, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the subject matter presented herein are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
General Description
The sensor chip includes the combination of a waveguide SPR sensor and a waveguide based interferometer on a single chip. The sensor chip is fabricated by depositing an optical waveguide core material with a thickness ranging from about 2 to about 20 μm with a high index of refraction onto a low index layer or substrate by chemical vapor deposition or a similar process, such as for example, flame hydrolysis. Through mask and etch steps, channel waveguides and other waveguide structures, for example, directional couplers and power splitters, are defined in the core material. An additional low index layer is deposited on top of the waveguide structure and the rest of the SPR chip to complete an optical channel waveguide.
The SPR sensor area is formed by etching down the top index layer to form a trench with dimensions between about 10 and about 100 μm in all directions that is coated with a thin metal film, such as gold or silver ranging in thickness from 0.001 um to 1 um thickness, to provide for the surface plasmon resonance. The sensor area or reservoir is small enough for the detection of chemical or biological agents down to micro-liter volumes, often down to about picoliter volumes. The SPR sensitive area is coated with specific antibodies, proteins, DNA sequences or amino acid sequences to provide for a functional layer that is sensitive and specific to chemical or biological agents of interest. By varying the thickness of the metal film or of the antibody layer enables the present invention to be used for linear detection or for threshold detection of predetermined bioagents.
The waveguide-based interferometer is fabricated through the formation of the optical waveguide structure as described above. The interferometer structure can include an array of single channel Mach-Zehnder (MZ) waveguide structures or an arrayed waveguide grating structure with a fixed optical path length difference.
In an array of single channel MZ structures, light having a wavelength ranging from about 300 nm to about 2000 nm, and more particularly about 800 nm for a gold metal film, is coupled into the input arm of the MZ waveguide structure. As another embodiment, a material substitution (e.g., silver instead of gold for the plasmon layer) enables a wavelength having a range between about 600 nm and about 650 nm to be deployed without departing from the scope of the invention. However, any wavelength range capable of producing plasmon resonance to the design parameters of the present may also be employed.
The majority of the light passes through the MZ arm with the SPR sensor while the rest of the light is sent through a reference arm of the MZ structure. Amplitude and phase of the light that is transmitted through the SPR sensor is altered for TM polarization and remains relatively unchanged for TE polarization. Amplitude and phase of the light passing through the reference MZ arm remains relatively unchanged. Both polarizations are then combined at the second coupler and the resulting intensity is substantially altered by the amplitude and phase change through SPR sensing waveguide. The MZ interferometer is designed with a built in bias for a predetermined application. A beneficial bias provides a nominal MZ phase shift of π radians. Such a design allows the intensity at the output waveguide to be half of the input intensity before any changes occur due to a detection event
Therefore, when a target molecule is absorbed by the functional sensing layer, the phase of the light in the SPR leg of the MZ structure is capable of changing by a value of up to π radians, and the output intensity drops to about zero. Such a device is beneficial for autonomous detection of biohazards or chemicals above a certain threshold, from which an alarm is capable of being triggered.
To compensate for temperature and mechanical stress induced changes in the MZ interferometer, the TE polarization that is transmitted through the same interferometer can be designed as a reference. The difference of TE vs. TM polarization is independent to any environmental changes and depends only on the sensing scheme. The TE and TM polarizations are capable of being separated and detected either externally through a polarization beam splitter or internally with a built-in waveguide based polarization beam splitter. Other beneficial biases are nominally near π/4 and 3π/4, placing the amplitude response of the MZ near its greatest slope where the sensitivity of the sensor will be at its greatest
A dual SPR cell can be designed and fabricated onto both arms of an MZ interferometer for eliminating the SPR amplitude and phase change due to bulk solution that carries the molecules for detection. However, only the SPR detection cell on the signal arm is functionalized with a capture layer to chemically bond to the target molecules. The SPR reference cell on the reference arm is identical to the SPR detection cell but without the functional sensing layer so that target molecules will not be absorbed to the SPR reference cell. The SPR reference cell is used to cancel the SPR amplitude change and phase shift due to the bulk solution, i.e. solvents, since the identical solution is placed onto both the detection and reference SPR cells. The net change of SPR amplitude and phase is the result of a target molecule being absorbed onto the capture layer of the detection cell. The absence of the SPR reference cell cancels the effect of an index change of the liquid solution due to ambient temperature fluctuations. In consequence, the detection of target molecules is greatly enhanced due to the elimination of a noisy background produced by, for example, such temperature fluctuations.
An SPR sensor based on an array of waveguides with different path-lengths can be produced from an array of SPR sensors arranged with a single waveguide input and output arm. Each waveguide SPR sensor is optically delayed in time, therefore a single scan of an external optical delay line simultaneously measures the amplitude and phase of each SPR sensor. Separation of any interferences from each SPR sensor in the array is achieved by use of a low coherence light source. A SPR reference cell is placed in the shortest optical delayed waveguide. To avoid changes due to temperature fluctuations, the wavelength stabilized light source accurately determines an optical path delay and further extracts the amplitude and phase of each SPR sensor separately. This single input arrayed waveguide SPR sensor simplifies multiple channel detection. A single interferometric scan allows the simultaneous recording of greater than about 1000 SPR sensors.
Specific Description
The sensor of the present invention couples an electromagnetic light source, such as, but not limited to, an LED or a laser, to the waveguide surface plasmon sensor structure as disclosed herein.
The fabrication method of the invention for creating sensor 100 includes: etching away cladding material 103 by methods known to those skilled in the art to create a trench 112 (as shown by the respective arrows in
As another embodiment, the optical waveguide structure, as shown in
The amplitude and phase change in optical delayed surface plasmon sensor arrays 800 also can be detected by an optical low coherence interferometer.
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Sep 18 2016 | YAN, MING | CYTEK BIOSCIENCES, INC | ASSIGNMENT OF ASSIGNORS INTEREST SEE DOCUMENT FOR DETAILS | 039899 | /0738 |
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